学科分类
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7 个结果
  • 简介:Neurodegenerativedisordersaffectmorethan30millionindividualsthroughouttheworldandleadtosignificantdisabilityaswellasdeath.Thesestatisticswillincreasealmostexponentiallyasthelifespanandageofindividualsincreasegloballyandindividualsbecomemoresusceptibletoacutedisorderssuchasstrokeaswellaschronicdiseasesthatinvolvecognitiveloss,Alzheimer’sdisease,andParkinson’sdisease.Currenttherapiesforsuchdisordersareeffectiveonlyforasmallsubsetofindividualsorprovidesymptomaticreliefbutdonotalterdiseaseprogression.Oneexcitingtherapeuticapproachthatmayturnthetideforaddressingneurodegenerativedisordersinvolvesthemammaliantargetofrapamycin(mTOR).mTORisacomponentoftheproteincomplexesmTORComplex1(mTORC1)andmTORComplex2(mTORC2)thatareubiquitousthroughoutthebodyandcontrolmultiplefunctionssuchasgenetranscription,metabolism,cellsurvival,andcellsenescence.mTORthroughitsrelationshipwithphosphoinositide3-kinase(PI3-K)andproteinkinaseB(Akt)andmultipledownstreamsignalingpathwayssuchasp70ribosomalS6kinase(p70S6K)andprolinerichAktsubstrate40kDa(PRAS40)promotesneuronalcellregenerationthroughstemcellrenewalandoverseescriticalpathwayssuchasapoptosis,autophagy,andnecroptosistofosterprotectionagainstneurodegenerativedisorders.TargetingbymTORofspecificpathwaysthatdrivelong-termpotentiation,synapticplasticity,andβ-amyloidtoxicitymayoffernewstrategiesfordisorderssuchasstrokeandAlzheimer’sdisease.Overall,mTORisanessentialneuroprotectivepathwaybutmustbecarefullytargetedtomaximizeclinicalefficacyandeliminateanyclinicaltoxicsideeffects.

  • 标签: 神经再生 目标驱动 哺乳动物 雷帕霉素 神经退行性疾病 阿尔茨海默氏病
  • 简介:Therearecurrentlynofederallyapprovedneuroprotectiveagentstotreattraumaticbraininjury.Progesterone,ahydrophobicsteroidhormone,hasbeenshowninrecentstudiestoexhibitneuroprotectiveeffectsincontrolledcorticalimpactratmodels.Aktisaproteinkinaseknowntoplayaroleincellsignalingpathwaysthatreduceedema,inflammation,apoptosis,andpromotecellgrowthinthebrain.ThisstudyaimstodetermineifprogesteronemodulatesthephosphorylationofAktviaitsthreonine308phosphorylationsite.Phosphorylationatthethreonine308siteisoneofseveralsitesresponsibleforactivatingAktandenablingtheproteinkinasetocarryoutitsneuroprotectiveeffects.ToassesstheeffectsofprogesteroneonAktphosphorylation,C57BL/6miceweretreatedwithprogesterone(8mg/kg)at1(intraperitonally),6,24,and48hours(subcutaneously)postclosed-skulltraumaticbraininjury.Thehippocampuswasharvestedat72hourspostinjuryandpreparedforwesternblotanalysis.TraumaticbraininjurycausedasignificantdecreaseinAktphosphorylationcomparedtoshamoperation.However,micetreatedwithprogesteronefollowingtraumaticbraininjuryhadanincreaseinphosphorylationofAktcomparedtotraumaticbraininjuryvehicle.Ourfindingssuggestthatprogesteroneisaviabletreatmentoptionforactivatingneuroprotectivepathwaysaftertraumaticbraininjury.

  • 标签: 创伤性脑损伤 磷酸化位点 保护作用 AKT 海马 显示
  • 简介:Vagusnervestimulationexertsprotectiveeffectsagainstischemicbraininjury;however,theunderlyingmechanismsremainunclear.Inthisstudy,aratmodeloffocalcerebralischemiawasestablishedusingtheocclusionmethod,andtherightvagusnervewasgivenelectricalstimulation(constantcurrentof0.5mA;pulsewidth,0.5ms;frequency,20Hz;duration,30seconds;every5minutesforatotalof60minutes)30minutes,12hours,and1,2,3,7and14daysaftersurgery.Electricalstimulationofthevagusnervesubstantiallyreducedinfarctvolume,improvedneurologicalfunction,anddecreasedtheexpressionlevelsoftumornecrosisfactor-αandinterleukin-6inratswithfocalcerebralischemia.Theexperimentalfindingsindicatethattheneuroprotectiveeffectofvagusnervestimulationfollowingcerebralischemiamaybeassociatedwiththeinhibitionoftumornecrosisfactor-αandinterleukin-6expression.

  • 标签: 局灶性脑缺血 缺血性脑损伤 迷走神经 电刺激 机制 肿瘤坏死因子
  • 简介:Therearefewstudiesontheneuroprotectiveeffectsofsyringaldehydeinaratmodelofcerebralischemia.Thestudyaimedtoelucidatethemechanismsunderlyingtheneuroprotectiveeffectsofsyringaldehydeonischemicbraincells.Ratmodelsofcerebralischemiawereintraperitoneallyadministeredsyringaldehyde.At6and24hoursaftersyringaldehydeadministration,celldamageinthebrainofcerebralischemiaratswasobviouslyreduced,superoxidedismutaseactivityandnuclearrespiratoryfactor1expressioninthebraintissueweremarkedlyincreased,malondiadehydelevelwasobviouslydecreased,apoptosis-relatedcysteinepeptidasecaspase-3and-9immunoreactivitywasobviouslydecreased,andneurologicalfunctionwasmarkedlyimproved.Thesefindingssuggestthatsyringaldehydeexertsneuroprotectiveeffectsoncerebralischemiainjurythroughanti-oxidationandanti-apoptosis.

  • 标签: 神经保护作用 细胞损伤 脑缺血 抗凋亡 抗氧化 丁香
  • 简介:1-methyl-4-phenylpyridiniumion(MPP+)inducesendoplasmicreticulumstressandactivatescaspase-12inPC12cells,leadingtoneuronalapoptosis.However,theunderlyingmolecularmechanismremainsunknown.Thepresentstudyinvestigatedtheregulatoryeffectsofnervegrowthfactor(Aktactivator)andlithiumchloride(glycogensynthasekinase-3βinhibitor)ontheendoplasmicreticulumstresssignalingpathway.TheresultsrevealedthatMPP+inducedexpressionofBipandC/EBPhomologousprotein.TheupregulationofBipandC/EBPhomologousprotein,aswellasthedecreasedpro-caspase-12levelinducedbyMPP+wereinhibitedbypretreatmentofthenervegrowthfactororlithiumchloride.Theseresultssuggestthatthephosphatidylinositol3kinase-Akt-glycogensynthasekinase-3βpathwayisinvolvedinMPP+-inducedendoplasmicreticulumstress.

  • 标签: 内质网应激 PC12细胞 诱导表达 激酶 合酶 糖原
  • 简介:Ischemicpreconditioningelicitedbyanon-fatalbriefocclusionofbloodflowhasbeenappliedforanexperimentaltherapeuticstrategyagainstasubsequentfatalischemicinsult.Inthisstudy,weinvestigatedtheneuroprotectiveeffectsofischemicpreconditioning(2-minutetransientcerebralischemia)oncalbindinD28kimmunoreactivityinthegerbilhippocampalCA1areafollowingasubsequentfataltransientischemicinsult(5-minutetransientcerebralischemia).AlargenumberofpyramidalneuronsinthehippocampalCA1areadied4daysafter5-minutetransientcerebralischemia.IschemicpreconditioningreducedthedeathofpyramidalneuronsinthehippocampalCA1area.CalbindinD28kimmunoreactivitywasgreatlyattenuatedat2daysafter5-minutetransientcerebralischemiaanditwashardlydetectedat5dayspost-ischemia.IschemicpreconditioningmaintainedcalbindinD28kimmunoreactivityaftertransientcerebralischemia.Thesefindingssuggestthatischemicpreconditioningcanattenuatetransientcerebralischemia-causeddamagetothepyramidalneuronsinthehippocampalCA1areathroughmaintainingcalbindinD28kimmunoreactivity.

  • 标签: 海马CA1区 锥体神经元 缺血预处理 神经保护作用 免疫反应性 钙结合蛋白